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Combined toxicity of fluoride and benzene hexachloride to rats
Abstract
Sprague-Dawley rats were given various treatments of 10 ppm fluoride, 25 ppm fluoride, 25 ppm benzene hexachloride (BHC), 10 ppm fluoride + 25 ppm BHC, or 25 ppm fluoride + 25 ppm BHC for 16 weeks ad libitum. Rats showed a decrease in body weight gain, which could be attributable to BHC alone. A synergistic effect of fluoride and BHC was seen only in females given 25 ppm fluoride + 25 ppm BHC: a decrease in red blood cells (RBC) and relative weight of the ovary. Females were more susceptible to the toxicity of fluoride and BHC than males.
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Age, diet and ethnic-dependent excretion of chlorinated pesticides through placenta and milk was studied in women from the general population around Lucknow in India by using gas-liquid chromatography equipped with an electron-capture detector (3H+). Pesticidal contaminants in both placenta and milk were 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), its metabolites 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDD), alpha, beta, gamma - isomers of benzene hexachloride (BHC) and aldrin. The study revealed higher excretion of pesticides through the placentas of older and non-vegetarian women than younger and vegetarian women. There was higher excretion of total DDT in rural than in urban women while a reverse trend was found in the case of total BHC in two ethnic groups. Similarly, age and dietary habits influenced the excretion of these pesticides in milk. Women undergoing premature delivery and stillbirths were found to excrete more DDT in their milk than those undergoing full-term normal delivery.
Mice were administered daily 17.3 and 5.2 mg F/kg b.w. (1/3rd and 1/10th LD50, respectively) orally from day 6 of mating until day 15 (10 days). Body weight and amount of food consumed were measured daily, until day 21, when the experiment was terminated. Fluoride-treated mice showed no sign of pregnancy; body weight and RBC counts declined. Hemoglobin declined significantly in mice given 5.2 mg F/kg b.w.
Rats given sodium fluoride at 10 mg/kg daily by the intraperitoneal route were more sensitive to the convulsant action of strychnine and pentylenetetrazol and to electroshock. This increase in sensitivity to CNS stimulation was observed also in two other groups of rats which were given a diet with added sodium fluoride amounting to 7 and 70 parts per million in terms of fluoride. Prolonged treatment with fluoride also lengthened the sleeping time induced by pentobarbital and increased the protective effect of diphenylhydantoin against electroshock. The increase in sensitivity to some CNS-active agents in the fluoride-treated rats disappeared after these rats were given the control diet for 2 weeks.
Dermal application of benzene hexachloride in daily doses of 100, 200 and 500 mg/kg for a total period of 30 days caused significant changes in male guinea pigs. The animals exposed to high doses of benzene hexachloride (1,2,3,4,5,6-hexachlorocyclohexane) (BHC) (BHC) died within 5--12 days. There was no mortality in 100 mg/kg/day but significant pathologic and biochemical changes were observed in the vital organs of the experimental animals. Massive congestion and thickened blood vessels were seen in liver of the BHC treated animals in comparison to the normal picture of the controls. Similarly, testicular changes included mild to severe pathologic lesions. There was no change in the epididymis, kidney, spleen, brain and lungs. The changes in the skin were mild and no signs of dermatitis were observed in the BHC painted areas. The activity of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase in liver and serum revealed significant changes from that of the controls. The significance of biochemical changes with the tissue damage of the insecticide exposed animals are discussed.
Inbred Swiss mice were treated with technical BHC (1) orally with the diet or by intubation and (2) by skin painting. The total duration of the experiment was 80 weeks. There was no difference in body growth and mortality between the experimental and control groups. Symptoms of intoxication in the form of convulsions and tendency of circling in one direction with drooping ears were observed alongwith corneal opacity 40 weeks after the experiment. Oral BHC treatment resulted in a significant increase in the incidence of liver tumours and tumours of lymphoreticular tissue. Males and females were equally susceptible. Skin painting of mice did not significantly increase the incidence of tumour.
In India organochlorine insecticides such as DDT and HCH constitute more than 70% of the pesticides used at present. Its continued use has given interest to monitor for the last few years the extent of organochlorine insecticide residues in soil, water, air and rain water in Delhi area. Out of the 50 samples each of soil and earthworms collected from different parts 48 samples showed that soil and earthworms contained 0-2.61 and 0-37.74 mg Kg-1 of total DDT residues respectively. The area near the vicinity of the DDT factory showed high levels of DDT residues. A two-year survey of the Yamuna river in Delhi showed that water contained an average of 0.24 ug L-1 and the bottom sediment had 0.24 mg Kg-1 of total DDT residues. The fishes collected from the Yamuna river showed very high bioaccumulation of DDT residues. The air and rainwater samples monitored from 3 different areas for two years indicated that DDT was more near the DDT factory area while HCH was more near a commercial complex. These results indicate that the overall organochlorine-residue levels in Delhi is not alarming. It probably indicates that DDT and HCH are more rapidly dissipated and degraded in a tropical country like India.